Previous studies have shown that pulmonary macrophages accumulate at sites of asbestos deposition on alveolar surfaces. Pulmonary macrophages are believed to play a central role in the pathogenesis of asbestosis. Accordingly, we have carried out a series of experiments designed to elucidate the initial chemotactic stimulus which attracts macrophages to sites of asbestos deposition where early lesions are known to develop. Four sets of experiments were carried out: 1) Peripheral blood serum from rats was mixed with chrysotile asbestos or zymosan, and a chemotactic factor (probably C5a) for macrophages was activated by both materials (chemotaxis is assayed by counting the numbers of cells migrating through a polycarbonate filter). 2) Proteins concentrated (2.4 mg/ml) from the lung lavage fluids of asbestos-exposed rats showed a significant increase in chemotactic activity compared to concentrates from sham-exposed animals. 3) A chemotactic factor was activated by adding asbestos or zymosan in vitro to protein lavaged from the lungs of normal, untreated rats. 4) C5-deficient mice exposed to asbestos exhibited significantly fewer macrophages on alveolar duct bifurcations compared to normal mice. We hypothesize that inhaled asbestos activates C5a on alveolar surfaces, and this well known chemotactic factor attracts local populations of alveolar macrophages. Biochemical studies to prove this hypothesis are ongoing to separate the lavaged fluid into fractions based on molecular weight (M.W.). Each of the fractions will be tested for chemotactic activity in attempts to support the hypothesis that the major chemotactic stimulus will be in the 15-20,000 m.w. range (i.e., C5a).